Abstract
Congenital tooth agenesis is a common anomaly in human development. We performed exome sequence analysis of genomic DNA collected from Japanese patients with tooth agenesis and their relatives. We found a novel single-nucleotide insertion in the LRP6 gene, the product of which is involved in Wnt/β-catenin signaling as a coreceptor for Wnt ligands. The single-nucleotide insertion results in a premature stop codon in the extracellular region of the encoded protein.
Highlights
Tooth agenesis is one of the most common developmental anomalies in humans; its underlying cause is complex and remains largely unknown
We have previously reported that the prevalence rates of hypodontia and oligodontia, which are subtypes of the condition, in the Japanese population are 6.8% and 0.1%, respectively; we found that sibling recurrence risks corresponded to 25.0% and 43.8%, respectively
Multiple congenitally missing teeth have been associated with abnormalities in several genes encoding Msh homeobox 12–5, ectodysplasin A6,7, axin inhibition protein 28, paired box gene 99, Wnt family member 10A (WNT10A)[10,11], and low-density lipoprotein receptor-related protein 6 (LRP6)
Summary
Hiroki Goto[1,2,3], Masashi Kimura[1,4,5], Junichiro Machida[1,6], Akiko Ota[7], Mitsuko Nakashima 5, Naomi Tsuchida[5,8], Junya Adachi[1,3], Yoshihiko Aoki[1,3], Tadashi Tatematsu[1,3], Katsu Takahashi[9], Masatoshi Sana[10], Atsuo Nakayama[11], Shintaro Suzuki[1,2], Toru Nagao[1], Naomichi Matsumoto[8] and Yoshihito Tokita 1,3 ✉. 12 functionally null variants of the LRP6 gene have been identified in families with congenital tooth agenesis[12,13,14,15]. We performed whole-exome sequencing (WES) as previously described[16] using genomic DNA from a Japanese family with congenital tooth agenesis and identified a novel frameshift mutation in LRP6. Several studies have revealed that loss-of-function mutations in LRP6 cause the autosomal dominant form of selective tooth agenesis (STHAG7: MIM 616724)[12,13,14,15]. We identified a novel LRP6 variant, c.1924dup, in a Japanese family with tooth agenesis. 1234567890();,: Fig. 2 LRP6 (low-density lipoprotein receptor-related protein 6 gene) mutation cosegregates with tooth agenesis.
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